Previous attempts to elucidate whether a loss of hippocampal synapses occurs during aging provided conflicting results, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. This study was designed to reexamine the issue by means of modern technical procedures that provide unbiased estimates of synaptic numbers. Groups of 14 young adult (5 months old) and 14 aged (28 months old) male Fischer-344 rats were compared. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus, where synaptic contacts are predominantly formed by different systems of afferents, the entorhinal and commissural-associational fibers, respectively. The number of synapses per neuron was estimated with the aid of the stereological dissector technique. The results showed that the total number of synaptic contacts per neuron was significantly diminished in the MML (by 23.6%) and IML (by 22.7%) of aged rats relative to young adults. This age-related synaptic loss involved axospinous, but not axodendritic, junctions of the MML (-24.4%) and IML (-24.0%). Both perforated and nonperforated axospinous synapses (distinguished by a discontinuous or continuous postsynaptic density, respectively) exhibited an age-dependent decrease in numbers, though this decrease did not reach statistical significance in the case of perforated junctions of the IML. The observed age-related loss of axospinous synapses may underlie the reduction in the amplitude of excitatory postsynaptic potentials and the decline in functional synaptic plasticity detected in the dentate gyrus of senescent rats.

Synapses were analyzed in the middle molecular layer (MML) and inner molecular layer (IML) of the rat dentate gyrus following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth high frequency stimulation. Stimulated but not potentiated and implanted but not stimulated animals served as controls. Using the stereological disector technique, unbiased estimates of the number of synapses per postsynaptic neuron were differentially obtained for various subtypes of axospinous junctions: For atypical (giant) nonperforated synapses with a continuous postsynaptic density (PSD), and for perforated ones distinguished by (1) a fenestrated PSD and focal spine partition, (2) a horseshoe-shaped PSD and sectional spine partition, (3) a segmented PSD and complete spine partition(s), and (4) a fenestrated, (5) horseshoe-shaped, or (6) segmented PSD without a spine partition. The major finding of this study is that the induction of LTP in the rat dentate gyrus is followed by a significant and marked increase in the number of only those perforated axospinous synapses that have multiple, completely partitioned transmission zones. No other synaptic subtype exhibits such a change as a result of LTP induction. Moreover, this structural alteration is limited to the terminal synaptic field of activated axons (MML) and does not involve an immediately adjacent one (IML) that was not directly activated by potentiating stimulation. The observed highly selective modification of synaptic connectivity involving only one particular synaptic subtype in the potentiated synaptic field may represent a structural substrate of the long-lasting enhancement of synaptic responses that characterizes LTP.

PurposeWhile there is strong evidence supporting the importance of telemedicine in stroke, its role in other areas of neurology is not as clear. The goal of this review is to provide an overview of evidence-based data on the role of teleneurology in the care of patients with neurologic disorders other than stroke.Recent findingsStudies across multiple specialties report noninferiority of evaluations by telemedicine compared with traditional, in-person evaluations in terms of patient and caregiver satisfaction. Evidence reports benefits in expediting care, increasing access, reducing cost, and improving diagnostic accuracy and health outcomes. However, many studies are limited, and gaps in knowledge remain.SummaryTelemedicine use is expanding across the vast array of neurologic disorders. More studies are needed to validate and support its use.

ObjectivePatients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.MethodsAmbulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded.ResultsEighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0–376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording.SignificanceAbout one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.

Changes in synaptic numbers were examined in the hippocampal dentate gyrus of aged (28 months old) rats following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats of the same chronological age served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the dentate gyrus. Using the stereological dissector technique, unbiased estimates of the number per neuron were obtained for the following morphological varieties of synapses: axodendritic synaptic junctions involving dendritic shafts, nonperforated axospinous synapses having a continuous postsynaptic density (PSD), and perforated ones distinguished by a fenestrated, horseshoe-shaped, or segmented PSD. The induction of LTP resulted in a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML), which was not directly stimulated during the induction of LTP. Comparison of these data with the results of our previous LTP study in young adult rats (Geinisman, Y. et al., 1991, Brain Res. 566:77-88) showed that the only significant difference in the absolute number of synaptic contacts per neuron between potentiated animals of the two chronological ages was an age-related reduction in segmented synapses of the MML. Relative increases in the number of segmented synapses per neuron were, however, virtually of the same magnitude in potentiated rats of both ages as compared with their respective controls. This finding may explain why senescent rats can be potentiated to the same extent as young ones.

Object Epilepsy surgery is at the cusp of a transformation due to the convergence of advancements in multiple technologies. Emerging neuromodulatory therapies offer the promise of functionally correcting neural instability and obviating the need for resective or ablative surgery in select cases. Chronic implanted neurological monitoring technology, delivered as part of a neuromodulatory therapeutic device or as a stand-alone monitoring system, offers the potential to monitor patients chronically in their normal ambulatory setting with outpatient medication regimens. This overcomes significant temporal limitations, pharmacological perturbations, and infection risks inherent in the present technology comprising subacute percutaneous inpatient monitoring of presurgical candidates in an epilepsy monitoring unit. Methods As part of the pivotal study for the NeuroPace Responsive Neurostimulation (RNS) System, the authors assessed the efficacy of the RNS System to control seizures in a group of patients with medically refractory epilepsy. Prior to RNS System implantation, these patients were not candidates for further resective surgery because they had temporal lobe epilepsy with bilateral temporal sources, frontal lobe reflex epilepsy with involvement of primary motor cortex, and occipital lobe epilepsy with substantial involvement of eloquent visual cortex. Without interfering with and beyond the scope of the therapeutic aspect of the RNS System study, the authors were able to monitor seizure and epileptiform activity from chronically implanted subdural and depth electrodes in these patients, and, in doing so, they were able to more accurately localize the seizure source. In 5 of these study patients, in whom the RNS System was not effective, the notion of resective surgery was revisited and considered in light of the additional information gleaned from the chronic intracranial recordings obtained from various permutations of electrodes monitoring sources in the frontal, temporal, parietal, and occipital lobes. Results Through long-term analysis of chronic unlimited recording electrocorticography (CURE) from chronically implanted electrodes, the authors were able to further refine seizure source localization and sufficiently increase the expected likelihood of seizure control to the extent that 4 patients who had previously been considered not to be candidates for surgery did undergo resective surgery, and all have achieved seizure freedom. A fifth patient, who had a double-band heterotopia, underwent surgery but did not achieve significant seizure reduction. Conclusions Chronic unlimited recording electrocorticography–guided resective epilepsy surgery employs new monitoring technology in a novel way, which in this small series was felt to improve seizure localization and consequently the potential efficacy of resective surgery. This suggests that the CURE modality could improve outcomes in patients who undergo resective surgery, and it may expand the set of patients in whom resective surgery may be expected to be efficacious and therefore the potential number of patients who may achieve seizure freedom. The authors report 4 cases of patients in which this technique and technology had a direct role in guiding surgery that provided seizure freedom and that suggest this new approach warrants further study to characterize its value in presurgical evaluation. Clinical trial no.: NCT00572195 (ClinicalTrials.gov).

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.